具有免疫抑制作用的含有聚乙二醇基的青蒿素衍生物的合成

Synthesis and immunosuppressive activity of new artemisinin derivatives containing polyethylene glycol group

摘要: 目的寻找免疫抑制活性更高的青蒿素类化合物。方法以二氢青蒿素为原料，通过缩合、酯化反应合成两类含有聚乙二醇基的青蒿素衍生物，测定它们对体外T细胞和B细胞增殖的抑制活性。结果合成了23个含有聚乙二醇基的青蒿素衍生物(2a～2f，3a～3d，4a～4f，6a，6b和7a～7g)，通过¹H NMR和元素分析确定其化学结构。结论这些化合物都有一定的体外免疫抑制活性。青蒿素母核对称取代2和6的活性高于青蒿素母核单取代的3，4和7。化合物2a～2f的活性比青蒿素、青蒿琥酯高。

Abstract: AimTo search for new artemisinin derivatives with higher immunosuppressive activity. MethodsTwo kinds of new artemisinin derivatives containing polyethylene glycol group were synthesized from dihydroartemisinin via condensation and esterification. These compounds were assayed for their inhibitory activity on ConA-induced T cell proliferation and LPS-induced B cell proliferation. Results Twenty three new compounds (2a-2f, 3a-3d, 4a-4f, 6a, 6b and 7a-7g) were synthesized and identified by ¹H NMR and elemental analysis. ConclusionThese compounds had immunosuppressive activity in vitro. Among them, the symmetrical substituted compound 2 and 6 had higher activity than mono-substituted compound 3, 4 and 7. Especially, compounds 2a-2f remarkably exhibited higher inhibition in comparison with artemisinin and artesunate.